Magnetic Particle Resuspension Probe Module

ABSTRACT

An acid injection module ( 100 ) comprising a dual probe nozzles ( 102 ).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Prov. Appl. No. 60/574,000,filed May 24, 2004, the entirety of which is hereby incorporated byreference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

N/A

BACKGROUND OF THE INVENTION

Heterogeneous immunoassays typically require the separation ofsought-for components bound to component-selective particles fromunbound or free components of the assay. To increase the efficiency ofthis separation, many assays wash the solid phase (the bound component)of the assay after the initial separation (the removal or aspiration ofthe liquid phase). Some chemiluminescent immunoassays use magneticseparation to remove the unbound assay components from the reactionvessel prior to addition of a reagent used in producingchemiluminescence or the detectable signal indicative of the amount ofbound component present. This is accomplished by using magnetizableparticles including, but not restricted to, paramagnetic particles,superparamagnetic particles, ferromagnetic particles and ferrimagneticparticles. Tested-for assay components are bound to component-specificsites on magnetizable particles during the course of the assay. Theassociated magnetizable particles are attracted to magnets for retentionin the reaction vessel while the liquid phase, containing unboundcomponents, is aspirated from the reaction vessel.

Washing of the solid phase after the initial separation is accomplishedby dispensing and then aspirating a wash solution, such as de-ionizedwater or a wash buffer, while the magnetizable particles are attractedto the magnet.

Greater efficiency in washing may be accomplished by moving the reactionvessels along a magnet array having a gap in the array structureproximate a wash position, allowing the magnetizable particles to beresuspended during the dispense of the wash solution. This is known asresuspension wash. Subsequent positions in the array include additionalmagnets, allowing the magnetizable particles to recollect on the side ofthe respective vessel.

Once the contents of the reaction vessel have again accumulated in apellet on the side of the reaction vessel and the wash liquid has beenaspirated, it is desirable to resuspend the particles in an acid reagentused to condition the bound component reagent. In the prior art, asingle stream of acidic reagent is injected at the pellet. Because thesize of the pellet and limitations on the volume and flow rate ofreagent, insufficient resuspension may result. To address thisinadequacy, prior art systems have resorted to the use of an additionalresuspension magnet disposed on an opposite side of the process pathfrom the previous separation magnets. The resuspension magnet isconfigured to assist in drawing paramagnetic particles into suspension,though the magnetic field is insufficient to cause an aggregation ofparticles on the opposite side of the vessel from where the pellet hadbeen formed. In addition, since the prior art approach utilizes aresuspension magnet, there is less motivation to accurately aim the acidresuspension liquid. Any inhomogeneity in the suspended particles isaddressed by the resuspension magnet.

It would be preferable to provide a system in which the use of aresuspension magnet is obviated.

BRIEF SUMMARY OF THE INVENTION

An improved acid injection module includes dual, parallel injectionprobes. A high-precision aiming strategy is employed to ensure thatcomplete, homogenous resuspension of accumulated solid-phase particlesis achieved, obviating the need for subsequent resuspension magnetpositions.

The dual, parallel injector probe nozzles are spaced by a degreenecessary to provide substantially adjacent impact zones on the reactionvessel wall, also referred to as “hit zones” or “hit points.” Throughcareful control over lateral spacing of the two nozzles, and thus thetwo hit zones, and by performing an exacting analysis of the variousphysical tolerances which can effect hit zone location relative to thesolid-phase pellet, thorough resuspension can be achieved without use ofa resuspension magnet.

Other features, aspects and advantages of the above-described method andsystem will be apparent from the detailed description of the inventionthat follows.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The invention will be more fully understood by reference to thefollowing detailed description of the invention in conjunction with thedrawings of which:

FIG. 1 illustrates an optimal orientation of resuspension probesrelative to a reaction vessel according to the presently disclosedinvention;

FIG. 2 illustrates certain physical parameters employed in defining theoptimal orientation of the probes of FIG. 1;

FIG. 3 illustrates additional physical parameters employed in definingthe optimal orientation of the probes of FIG. 1;

FIG. 4 illustrates additional physical parameters employed in definingthe optimal orientation of the probes of FIG. 1;

FIG. 5 illustrates additional physical parameters employed in definingthe optimal orientation of the probes of FIG. 1;

FIG. 6 pictorially illustrates system components which contributevertical tolerances and which must be accommodated in defining theoptimal probe orientation of FIG. 1;

FIG. 7 is a vector diagram representation of the tolerance contributorsof FIG. 6;

FIG. 8 pictorially illustrates system components which contributehorizontal tolerances and which must be accommodated in defining theoptimal probe orientation of FIG. 1;

FIG. 9 is a vector diagram representation of the tolerance contributorsof FIG. 8

FIG. 10 is a perspective view of a probe module according to thepresently disclosed invention;

FIG. 11 is a front view of the probe module of FIG. 10;

FIG. 12 is a section view of the probe module of FIGS. 10 and 11 takenalong lines A-A; and

FIG. 13 is a section view of the probe module of FIGS. 10 and 11 takenalong lines B-B.

DETAILED DESCRIPTION OF THE INVENTION

The presently disclosed concept finds particular applicability toautomated laboratory analytical analyzers in which paramagneticparticles are drawn into a pellet on the side of a reaction vessel aspart of a separation and wash process. In particular, in an analyzer inwhich chemiluminescence is utilized for determining analyteconcentration, the accumulated particles must be thoroughly resuspendedto obtain an accurate reading. One approach in such systems is toresuspend the accumulated, washed particles in acid prior to introducinga base, and thus triggering the chemiluminescent response, at an opticalmeasuring device such as a luminometer. However, it is noted that thepresently disclosed concept is also applicable to any environment inwhich thorough resuspension of accumulated particles is required.

FIG. 1 illustrates a reaction vessel (also referred to as a cuvette), aprobe nozzle, and the ideal orientation of the probe with respect to thecuvette. Note that two probes are employed, though only one is visiblein the profile illustrated of FIG. 1. Linear distance values are givenin millimeters. As shown, the ideal distance below the cuvette top planewhere the liquid stream hits the cuvette wall, referred to as the hitpoint, is 25.98 mm. In the illustrated embodiment, this hit point is5.74 mm above the centerline of a magnet array which forms the solidspellet and represents an empirically determined ideal locus of the hitpoint for achieving thorough particle resuspension. The probe is angled6.9 degrees from vertical, with the probe tip being located 0.92millimeters behind the cuvette centerline and 2.304 mm above the cuvettetop plane. These values are obtained, as described below, by calculatingthe worst-case tolerance errors which could effect the hit point and byfinding the locus where, even assuming all tolerances have a maximumdeviation, the hit point will still be above the magnet centerline.

One practical aspect not accounted for in the configuration described inFIG. 1 is the effect of gravity on the liquid stream itself. The idealhit point illustrated in FIG. 1 is calculated by extending the axis ofthe probe towards the cuvette wall. Because of the effect of gravity,the actual hit point is slightly below the one illustrated in FIG. 1.That distance is calculated in the following.

With respect to FIG. 2, given values include:

Pump flow rate V = 1300 μl/s Probe inner diameter id = 0.65 mm Probeinclination from vertical φ = 6.9° Vertical probe tip to hit point h =27.868 mm Axial probe tip to hit point l = 28.071 mm

The speed v₀ of the liquid at the probe tip can be derived from the pumpflow rate and the needle inner diameter:

A = π r² = π(0.325  mm)² = 0.332  mm²$v_{0} = {\frac{\overset{.}{V}}{A} = {\frac{1300\mspace{14mu} {µl}\text{/}s}{0.332\mspace{14mu} {mm}^{2}} = {\frac{1300\mspace{11mu} \frac{{mm}^{3}}{s}}{0.332\mspace{14mu} {mm}^{2}} = {{3915\mspace{11mu} \frac{mm}{s}} = {3.91\mspace{14mu} \frac{m}{s}}}}}}$

With reference to FIG. 2, the horizontal distance between the probe tipand the cuvette wall can be calculated from:

s=√{square root over (l² −h ²)}

s=3.37 mm=3.37 ·10⁻³m

With reference to FIG. 3, the arc of the liquid stream can now becalculated:

${{with}\mspace{14mu} h^{\prime}} = {{{v_{0}t\; \sin \; \alpha^{\prime}} - {\frac{g}{2}t^{2}\mspace{14mu} {and}\mspace{14mu} t}} = \frac{s}{v_{0}\cos \; \alpha^{\prime}}}$$\begin{matrix}{\left. \Rightarrow h^{\prime} \right. = {{s\; \frac{\sin \; \alpha^{\prime}}{\cos \; \alpha^{\prime}}} - {\frac{g}{2}\left( \frac{s}{v_{0}\cos \; \alpha^{\prime}} \right)^{2}}}} \\{= {{s\; \tan \; \alpha^{\prime}} - {\frac{g}{2}\left( \frac{s}{v_{0}\cos \; \alpha^{\prime}} \right)^{2}}}} \\{= {{{2.78 \cdot 10^{2}}\mspace{14mu} m} - {{2.52 \cdot 10^{- 4}}\mspace{11mu} m}}}\end{matrix}$

The first part of the term is equal to h and the second part gives thedifference between the ideal shown in FIG. 1 and actual hit point.

Overall, there are four tolerance chains which can affect the hit point:

-   -   1) Height tolerances—Tolerance summation of parts which affect        the vertical gap between the probe tip and the cuvette top        plane;    -   2) Axial tolerances—Tolerance summation of parts which affect        the horizontal or axial gap between the probe tip and the        central axis of the cuvette;    -   3) Angle tolerances—Tolerance summation of parts which affect        the probe injection angle (any angle tolerances of the cuvette        transport system are considered to result in a height error and        therefore are considered part of the height tolerance chain);        and    -   4) Magnet array—Tolerance summation of parts which affect the        vertical distance between the cuvette and the magnet array        centerline.

In the following, every tolerance chain is treated individually.Eventually, the total tolerance is estimated by adding the results ofthe individual tolerance chains.

The calculations for the individual tolerance chains are performed byexecuting the following steps:

Identification of related parts and their respective tolerances,providing a graphical description of the tolerance chain;

Graphical vector analysis of the tolerance chain;

Generation of a table of dimensions, tolerances, maximum dimensions,minimum dimensions;

Calculation of the ideal closure dimension;

Calculation of the arithmetic maximum and minimum closure dimensions andthe arithmetic tolerance;

Identification of mean values from asymmetric tolerance zones and meansvalues of shape and positional tolerances;

Generation of closure dimension as distribution average;

Identification of deviation σ/variance σ² for every dimension andcalculation of the total error according to the theorem of errorpropagation; and

Evaluation of statistical closure dimension and tolerance.

The dimensions of all parts are considered to have normal, Gaussiandistributions with a deviation of ±3σ. This means that 99.73% of allparts are inside the tolerance zone. This assumption is realistic forlot sizes of 60 to 100 parts and greater. The shape and positiontolerances have a folded normal distribution.

For statistical calculation of the hit point tolerance, a mathematicaldescription of the hit point depending upon linear position and angle ofthe probe is necessary. The arc of the liquid stream is omitted at thispoint for simplicity, but is factored in subsequently.

A simplified arrangement of a probe module and cuvette is shown in FIG.4. The draft or outward curvature of the cuvette wall is omitted. h isthe distance between the cuvette top plane and the hit point on theinner wall of the cuvette. The width of the cuvette is assumed to beconstant. cw thus gives half the width of the cuvette such that cw=2.73mm.

h = h_(g) − y${{and}\mspace{14mu} h_{g}} = \frac{x + {cw}}{\tan \; \phi}$$h = {\frac{x + {cw}}{\tan \; \phi} - y}$

The draft angle β, not taken into account in the foregoing, is 0.5°.

FIG. 5 illustrates the offset produced by the cuvette wall draft. Thevalue h_(r) has to be deducted from h to get the actual value of the hitpoint h_(real).

h_(real) = h − h_(r) with  h_(r) = l ⋅ cos  ϕ${{and}\mspace{14mu} l} = {\left. {{\frac{h}{\sin \left( {{180{^\circ}} - \beta - \phi} \right)} \cdot \sin}\; \beta}\Rightarrow h_{real} \right. = {\frac{x + {cw}}{\tan \; \phi} - y - \begin{bmatrix}{\left( {\frac{x + {cw}}{\tan \; \phi} - y} \right) \cdot} \\{{\frac{1}{\sin \left( {180 - \beta - \phi} \right)} \cdot \sin}\; {\beta \cdot \cos}\; \phi}\end{bmatrix}}}$

(Eq. 1). Substituting the projected values from FIG. 1 into x, y, and φas control gives the correct value for h_(real), 25.98 mm.

Height tolerances are now considered with respect to FIG. 6, whichillustrates all parts which add tolerances in height. These partsinclude a washer plate on which is mounted the acid injection probemodule, the probe module, a cuvette transport ring segment in which thecuvettes are disposed, and a transport ring on which the ring segmentsare disposed. The transport ring is supported by a taper roller bearingand opposing circlips. Both the washer plate and the taper rollerbearing/circlips are supported upon an incubation ring.

For the worst case in terms of height, it is assumed all tolerances areat their maximum, so that clearance between the washer plate and thecuvette is minimal. The hit point is thus lowered towards the bottom ofthe cuvette. To achieve this, parts of the left side of FIG. 6 must beat their minimum thickness whereas the parts on the right side must beat their maximum thickness. These requirements are illustrated in FIG. 6by the large arrows.

The vector diagram of FIG. 7 shows all dimensions with their maximizedor minimized direction. M0 is the so-called closure dimension, or thevertical gap between the probe tip and the cuvette upper plane. In theequations, this value is referred to as y. The const. vector sums thetwo constant values shown in FIG. 6, the thickness of the cuvette topplane and the vertical distance between the probe tip and the washerplate.

In the following table, all factors with the respective maximum andminimum values and resulting tolerance zones are provided:

Max. Min. vector Dimension dimension G_(o) dimension G_(u) Tolerancezone +const. 3.596 3.596 3.596 0 +M1 0 0.1 −0.1 0.2 −M2 90 90 89.95 0.05+M3 6.15 6.17 6.13 0.04 +M4 1.75 1.75 1.69 0.06 +M5 15 15.2 15 0.2 +M61.2 1.2 1.14 0.06 +M7 52 52.04 51.96 0.08 +M11 0 0.2 −0.2 0.4 +M8 0 0.2−0.2 0.4 +M9 5 5.1 4.9 0.2 +M10 3 3.1 2.9 0.2

The nominal closure dimension M_(OH):

M_(0H) = ∑M_(i+) − ∑M_(i−) $\begin{matrix}{M_{0H} = {3.596 + 0 - 90 + 6.15 + 1.75 +}} \\{{15 + 1.2 + 52 + 0 + 0 + 5 + 3}} \\{= {- 2.304}}\end{matrix}$

The arithmetic maximum closure dimension y_(max):

y_(max) = ∑G_(o_(i)+) − ∑G_(u_(i)−) $\begin{matrix}{y_{\max} = \left( {3.596 + 0.1 + 6.17 + 1.75 + 15.2 + 1.2 +} \right.} \\{\left. {52.04 + 0.2 + 0.2 + 5.1 + 3.1} \right) - 89.95} \\{= {- 1.294}}\end{matrix}$

The arithmetic minimum closure dimension y_(min):

y_(min) = ∑G_(u_(i)+) − ∑G_(o_(i)−) $\begin{matrix}{y_{\min} = \left( {3.595 + \left( {- 0.1} \right) + 6.13 + 1.69 + 15 + 1.14 + 51.96 +} \right.} \\{\left. {\left( {- 0.2} \right) + \left( {- 0.2} \right) + 4.9 + 2.9} \right) - 90} \\{= {- 3.184}}\end{matrix}$

The arithmetic closure dimension with tolerance zone is thus:

$M_{0H} = {y = {2.304\begin{matrix}{+ 0.88} \\{- 1.01}\end{matrix}}}$

Some statistical calculations are necessary to account for componentfluctuations. The mean values from asymmetric tolerance zones M2, M4, M5and M6 are now defined. For M2:

$\mu_{2} = {\frac{90 + 89.95}{2} = 89.975}$

Similar calculations for M4, M5, and M6 yield:

μ₄=1.72

μ₅=15.1

μ₆=1.17

As for M1, M8, and M11, shape and positional tolerances are distributedwith a folded normal distribution. Mean values and deviations musttherefore be calculated with the following equations. A deviation of 3σis thereby assumed.

$\begin{matrix}{{\sigma_{1} = {\frac{F_{1}}{3} = {\frac{0.2}{3} = 0.066}}}{\mu_{F\; 1} = {\frac{2\sigma_{1}}{\sqrt{2\pi}} = 0.053}}\sigma_{F\; 1} = {{\sqrt{1 - \frac{2}{\pi}} \cdot \sigma_{1}} = 0.04}} & {M1} \\\begin{matrix}{\sigma_{8} = 0.133} & {\mu_{8} = 0.106} & {\sigma_{F\; 8} = 0.08}\end{matrix} & {M8} \\\begin{matrix}{\sigma_{11} = 0.133} & {\mu_{11} = 0.106} & {\sigma_{F\; 11} = 0.08}\end{matrix} & {M11}\end{matrix}$

The closure dimension μ_(0H) is calculated as a distribution average:

3.596 + 0.053 − 89.975 + 6.15 + 1.72 + 15.1 + 1.17 + 52 + 0.106 + 0.106 + 5 + 3 = −1.974

The deviation σ_(0H) of the closure dimension:

$\sqrt{\begin{matrix}{0.04^{2} + \left( \frac{0.05}{6} \right)^{2} + \left( \frac{0.04}{6} \right)^{2} + \left( \frac{0.06}{6} \right)^{2} +} \\{\left( \frac{0.2}{6} \right)^{2} + \left( \frac{0.06}{6} \right)^{2} + \left( \frac{0.08}{6} \right)^{2} + 0.08^{2} +} \\{0.08^{2} + \left( \frac{0.2}{6} \right)^{2} + \left( \frac{0.2}{6} \right)^{2}}\end{matrix}} = 0.135$ T_(SH) = 6σ_(0H) = 0.81

The statistical closure dimension with tolerance zone is:

M _(0H) =y=μ _(0H)±(T _(SH)/2)=1.974±0.405

Axial tolerances are now considered. FIG. 8 illustrates the componentswhich contribute tolerances in the axial direction. The worst case isreached if the probes are displaced towards the inside of the incubationring and the cuvette is displaced away from the probes. The large arrowsin FIG. 8 illustrate these conditions.

The vector diagram of FIG. 9 the various contributing factors with therespective direction. M0 is the closure dimension, here the horizontalgap between the probe tip and the cuvette centerline. In the equationsthat follow, this value is identified as x.

The const. vector is the constant value shown in FIG. 8 and representsthe horizontal distance between the probe tip and the cuvettecenterline. The tolerance of this separation can be neglected due to theconstruction of a preferred instrument.

In the following table, all of the contributors with their maximum andminimum dimensions and tolerance zones are provided.

Max. Min. Vector Dimension dimension G_(o) dimension G_(u) Tolerancezone −const. 0.3 0.3 0.3 0 −M11 23.03 23.13 22.93 0.2 +M12 226 226.02225.98 0.04 −M13 0 −0.05 0.05 0.1 −M14 215.87 215.92 215.82 0.1 +M1514.12 14.22 14.02 0.2

The nominal closure dimension M_(0A) is given by:

M_(0A) = ∑M_(i+) − ∑M_(i−) − 0.3 − 23.03 + 226 − 0 − 215.87 + 14.12 = 0.92

The arithmetic maximum closure dimension x_(max) is given by:

x_(max) = ∑G_(o_(i)+) − ∑G_(u_(i)−)(226.02 + 14.22) − (0.3 + 22.93 + 0.05 + 215.82) = 1.14

The arithmetic minimum closure dimension x_(min) is given by:

x_(min) = ∑G_(u_(i)+) − ∑G_(o_(i)−)(225.98 + 14.02) − (0.3 + 23.13 + (−0.05) + 215.92) = 0.7

From these values, the arithmetic closure dimension with tolerance zoneis given by:

$M_{0\; A} = {x = {0.92\begin{matrix}{+ 0.22} \\{- 0.22}\end{matrix}}}$

Some statistical calculations are necessary to account for componentfluctuations. The mean values for shape and position for tolerance M13are now defined.

M13: σ₁₃=0.033 μ_(F13)=0.027 σ_(F13)=0.02

Closure dimension μ_(0A) is given as a distribution average:

−0.3−23.03+226−0.02−215.87+14.12=0.9

The deviation σ_(0A) of the closure dimension is determined from:

$\sqrt{\left( \frac{0.2}{6} \right)^{2} + \left( \frac{0.04}{6} \right)^{2} + 0.02^{2} + \left( \frac{0.1}{6} \right)^{2} + \left( \frac{0.2}{6} \right)^{2}} = 0.054$

The statistical closure dimension with tolerance zones is given by:

M _(0A) =x=μ _(0A) ±T _(SA)/2=0.9±0.162

Injector inclination tolerances are now addressed. The tolerance of thebores in the washer plate is M16=±0.05°. The parallelism of the axis ofthe probe bore and the axis of the injector outer diameter is M17=0.05mm. With the length of 18 mm this results in an angle tolerance of:

$\phi = {{M\; 16} + {\arctan \left( \frac{M\; 17}{18} \right)}}$Max. Min. Vector dimension dimension G_(o) dimension G_(u) Tolerancezero M16 6.9° 6.95° 6.85° 0.1° M17 0 0.05° −0.05° 0.1°

The nominal angle φ₀ is given by:

$\phi_{0} = {{{6.9{^\circ}} + {\arctan \left( \frac{0}{18} \right)}} = {6.9{^\circ}}}$

The arithmetic maximum angle φ_(max) is given by:

$\phi_{\max} = {{{6.85{^\circ}} + {\arctan \left( \frac{- 0.05}{18} \right)}} = {6.69{^\circ}}}$

The arithmetic minimum angle φ_(min) is given by:

$\phi_{\min} = {{{6.95{^\circ}} + {\arctan \left( \frac{0.05}{18} \right)}} = {7.11{^\circ}}}$

The closure dimension with tolerance zone is thus given by:

$\phi_{0} = {\phi = {6.9{^\circ}\begin{matrix}{+ 0.21} \\{- 0.21}\end{matrix}}}$

Some statistical calculations are necessary to account for componentfluctuation. The mean values for shape and position for tolerance M17are now defined.

M17: σ₁₇=0.033° μ_(F17)=0.027° σ_(F17)=0.02°

The average angle distribution μ_(0φ) is given by:

$\mu_{0\phi} = {{{6.9{^\circ}} + {\arctan \left( \frac{0.027{^\circ}}{18} \right)}} = {6.986{^\circ}}}$

The deviation of the angle error is given by:

$\begin{matrix}{\mu_{F\; 17} = {0.027{^\circ}}} & {\sigma_{M\; 16} = \left( \frac{0.1{^\circ}}{6} \right)} & {\sigma_{F\; 17} = {0.02{^\circ}}}\end{matrix}$ $\sigma_{0\phi} = \sqrt{\begin{matrix}{{\left\lbrack {\frac{}{{M}\; 16}\left( {{M\; 16} + {\arctan \left( \frac{\mu_{F\; 17}}{18} \right)}} \right)} \right\rbrack^{2}\sigma_{M\; 16}^{2}} +} \\{\left\lbrack {\frac{}{\mu_{F\; 17}}\left( {{M\; 16} + {\arctan \left( \frac{\mu_{F\; 17}}{18} \right)}} \right)} \right\rbrack^{2}\sigma_{F\; 17}^{2}}\end{matrix}}$ σ_(0 ϕ) = 0.017^(∘) T_(S) = 6 σ₀ = 0.102^(∘)

The statistical angle error with tolerance zone is thus given by:

$\phi_{0} = {\phi = {{\mu_{0} \pm \frac{T_{s}}{2}} = {{6.9{^\circ}} \pm {0.05{^\circ}}}}}$

The worst case calculation for hreal can now be calculated by settingthe arithmetic maximum values for x_(max), y_(max), and φ_(max) into Eq.1, above.

x_(max) = 1.14 y_(max) = 1.294 ϕ_(max) = 6.69^(∘)$h_{real} = {\frac{x + {cw}}{\tan (\alpha)} - y - \left\lbrack {\left( {\frac{x + {cw}}{\tan (\alpha)} - y} \right)\frac{1}{\sin \left( {\pi - \beta - \alpha} \right)}{\sin (\beta)}{\cos (\alpha)}} \right\rbrack}$h_(real) = 29.504

The arithmetic minimum can be calculated using the analog:

x_(min) = 0.7 y_(min) = 3.184 ϕ_(min) = 7.11^(∘)$h_{real} = {\frac{x + {cw}}{\tan (\alpha)} - y - \left\lbrack {\left( {\frac{x + {cw}}{\tan (\alpha)} - y} \right)\frac{1}{\sin \left( {\pi - \beta - \alpha} \right)}{\sin (\beta)}{\cos (\alpha)}} \right\rbrack}$h_(real) = 22.725

Thus, the arithmetic derivation of the hit point with tolerance zone isgiven by:

$h_{real} = {25.98\begin{matrix}{+ 3.52} \\{- 3.25}\end{matrix}}$

The hit point μ_(h) as distribution average with μ_(0H)=1.974,μ_(0A)=0.9, μ_(0φ)=6.986° and employing Eq. 1:

μ_(h)=25.812

The statistical deviation σ_(h) of the hit point, depending upon thevariables σ_(0A), σ_(0H), σ_(0φ), can now be calculated using Eq. 1.Using partial derivatives at the distribution average:

$\sigma_{h}^{2} = {{\left( \frac{\partial h_{real}}{\partial x} \right)^{2}\sigma_{0A}^{2}} + {\left( \frac{\partial h_{real}}{\partial y} \right)^{2}\sigma_{0H}^{2}} + {\left( \frac{\partial h_{real}}{\partial\phi} \right)^{2}\sigma_{0\phi}^{2}}}$

With μ_(0H)=1.974, μ_(0A)=0.9, μ_(0φ)=6.986° and σ_(0H)=0.135,σ_(0A)=0.054, and σ_(0φ)=0.017°, the result is:

σ_(h)=0.435

T_(SH)=6σ_(h)=2.61

The statistical error of the hit point with tolerance zone is thus givenby:

$h_{real} = {{25.98 \pm \frac{T_{SH}}{2}} = {25.98 \pm 1.305}}$

In the embodiment in which the pellet is formed by a magnet array, thetolerance of the array relative to the cuvettes must also be accountedfor. The magnets, in a preferred embodiment, are fixed in a ring whichis suspended under the transport ring. Most of the tolerance of themagnets is addressed in the height tolerances previously calculated.Thus, there are only the following tolerances to be accounted for:

M18—slide bearing;

M19—magnet ring (i.e. the position of the magnet assembly in the magnetring);

M20—magnet assembly (i.e. the tolerance of the fixture into which themagnet assembly is fixed); and

M21—the slide bearing support.

All of the above contribute to movement in the same direction.

Min. Tolerance Vector dimension Max. dimension G_(o) dimension G_(u)zone M18 4 4.1 4.05 0.05 M19 7.4 7.45 7.35 0.1 M20 0 0.05 −0.05 0.1 M211 1.1 0.9 0.2

The nominal closure dimension M_(0M) is given by:

M_(0M=ΣM) _(i)

4+7.4+1=12.4

The arithmetic maximum closure dimension P_(0M) is given by:

P_(0M=ΣG) _(0i)

4.1+7.45+0.05+1.1=12.7

The arithmetic minimum closure dimension P_(0M) is given by:

P_(0M=ΣG) _(0i)

4.05+7.35−0.05+0.9=12.25

The arithmetic closure dimension with tolerance zone is thus given by:

$M_{0M} = {12.4\begin{matrix}{+ 0.3} \\{- 0.15}\end{matrix}}$

Mean values from asymmetric tolerance zone M18 is given by:

μ₁₈=4.075

The closure dimension μ_(0M) as a distribution average is foundaccording to:

5.075+7.4+1=12.475

The deviation σ_(0M) of the closure dimension is given by:

$\sqrt{\left( \frac{0.05}{6} \right)^{2} + \left( \frac{0.1}{6} \right)^{2} + \left( \frac{0.1}{6} \right)^{2} + \left( \frac{0.2}{6} \right)^{2}} = 0.042$T_(SM) = 6σ_(0M) = 0.252

The statistical closure dimension with tolerance zone is thus:

$M_{0M} = {{\mu_{0M} \pm \frac{T_{SM}}{2}} = {12.475 \pm 0.126}}$

The nominal distance between the magnet centerline and the cuvette topplane at the acid injection position is 31.72 mm. This value can becalculated with the nominal dimensions listed above:

3.9+12.4+6.35+5+3+1.067=31.717

(3.9 being the distance between the upper magnet and the magnet ring,6.35 being the magnet width).

The deviation σ_(h) and the tolerance zone T_(SH) of the hit pointrelative to the cuvette top plane was estimated above as 25.98±1.305 mm.The nominal measure between hit point and magnet centerline is thus:

h _(total)=31.717−25.98=5.737

The total deviation σ of the difference between hit point and magnetcenterline is thus calculated by:

√{square root over (0.435²+0.042²)}=0.437

T_(s)=6σ=2.622

The statistical error of the hit point versus magnet centerline withtolerance zone can then be written as:

$h_{total} = {{5.737 \pm \frac{T_{s}}{2}} = {5.737 \pm 1.311}}$

Once 0.25 mm is added to compensate for the arc of the liquid stream,the acid injection is calculated to hit the cuvette wall not deeper than4.167 mm above the magnet centerline.

One embodiment of a probe housing 100 is illustrated in FIG. 10. Thishousing, which supports dual probe nozzles 102 is mounted in order todirect a parallel stream of liquid, preferably acid, above a pellet ofparticles such as paramagnetic particles which have accumulated on theinterior wall of a reaction vessel such as a cuvette. By following thetolerance analysis procedure detailed above, the hit point for both acidstreams can be assured to be above the pellet, regardless of variationsin the physical components of the system.

The linear dimensions in FIGS. 11, 12 and 13 are all given inmillimeters. A front view of the probe housing 100 is provided in FIG.11, showing the mutually adjacent nozzles which produce parallel streamsof resuspension liquid. In FIG. 12, a cross-section taken along linesA-A in FIG. 11, it can be seen that ideally a source of resuspensionliquid is coupled to the back of the probe housing. As can be seen inFIG. 13, a cross-section taken along lines B-B of FIG. 11, the liquidsource feeds both nozzles 102 in generating the parallel streams, fivemillimeters apart.

On the back of the probe housing 100 is a mounting recess 110 forinterfacing to a resuspension liquid-supplying conduit (not shown).Secure attachment of the conduit to the housing 100 is preferablythrough interlocking threads or other means known to one skilled in theart. Preferably a buffer zone 112 exists between the forward end of theconduit once installed in the recess 110. Liquid from the conduit passesinto the buffer zone and then into each of two channels 114 which leadto respective probes 116 and the probe nozzles 102 themselves. In theillustrated embodiment, the probes 116 and nozzles 102 are 0.65±0.02 mmin diameter.

Having described preferred embodiments of the presently disclosedinvention, it should be apparent to those of ordinary skill in the artthat other embodiments and variations incorporating these concepts maybe implemented. Accordingly, the invention should not be viewed aslimited to the described embodiments but rather should be limited solelyby the scope and spirit of the appended claims.

1. A resuspension nozzle module for enabling resuspension of accumulatedparticles in a reaction vessel comprising: a probe housing mountable inan analytical instrument; a mounting recess on a rear surface of theprobe housing for interfacing the module to a source of resuspensionliquid; plural channels, defined within the probe housing, in fluidcommunication with the mounting recess; plural probes, defined withinthe probe housing, each in fluid communication with a respective one ofthe channels; and plural probe nozzles, formed on a front surface of theprobe housing, each in fluid communication with a respective one of theprobes, wherein the plural probes and probe nozzles are mutuallyparallel.
 2. The resuspension nozzle module of claim 1 wherein theplural probe nozzles are configured to dispense parallel streams ofresuspension liquid.
 3. In an automated analysis system having at leastone resuspension liquid nozzle and serially conveyed reaction vessels inwhich solids particles are accumulated against an interior wall of eachreaction vessel and require resuspension, a method of verifying eachnozzle can project a stream of resuspension liquid within a target fieldon the interior wall of each reaction vessel relative to the accumulatedsolids particles, the method comprising the steps of: defining linearand angular dimensional offset values between the nozzle and the targetfield necessary for the resuspension liquid stream to hit the targetfield; for all system components having non-zero positional tolerancesin a respective dimension or dimensions, identifying the respectivepositional tolerance; determining the nominal value and tolerance forthe difference in the respective dimension or dimensions between thenozzle and the respective target as a closure value; calculating thetotal deviation of the closure value in the respective dimension ordimensions for all components having a non-zero positional tolerance inthe respective dimension; for all system components having an asymmetrictolerance distribution in the respective dimension or dimensions,determining the mean values and deviation for each; for all systemcomponents having a folded normal tolerance distribution in therespective dimension or dimensions, determining the mean values anddeviations for each; determining the statistical closure value withtolerance based upon the determined mean values and deviations and thecalculated total deviation in the respective dimension or dimensions;from the total deviation of the closure value in each dimension ordimensions, calculating the arithmetic deviation of the target; from thestatistical closure values in each dimension, estimating the totalstatistical deviation from the target; and from the total statisticaldeviation, deriving the statistical error from the target withtolerance.
 4. In an automated analysis system having at least oneresuspension liquid nozzle and serially conveyed reaction vessels inwhich solid particles are accumulated against an interior wall of eachreaction vessel, the solid particles requiring selective resuspension, amethod of verifying each nozzle can project a stream of resuspensionliquid within a target field on the interior wall of each reactionvessel relative to the accumulated solid particles, the methodcomprising the steps of: defining ideal linear and angular offset valuesfor the nozzle, relative to the cuvette, along vertical and horizontallinear dimensions and in the angular plane defined thereby, the ideallinear and angular offset values enabling resuspension liquid to impactthe cuvette within the target field; identifying all structuralcomponents contributing to tolerance stack-up in each linear dimensionand angular plane; identifying the nominal linear dimension or angularorientation and the tolerance range, if any, for each structuralcomponent in each linear dimension and angular plane, respectively;arithmetically calculating a nominal closure value for each lineardimension and angular plane as the difference between the ideal linearand angular offset values and the respective summed structural componentnominal linear and angular measurements; determining the tolerance rangefor the nominal closure value for each linear dimension and angularplane as the arithmetic sum of the respective tolerances of thestructural components in the respective linear dimension and angularplane; determining tolerance mean and deviation values for eachstructural component in each linear dimension and angular plane;statistically calculating the nominal closure value for each lineardimension and angular plane as a distributed average of the tolerancemean values of the respective structural components; statisticallycalculating the respective tolerance zone for each linear dimension andangular plane from the tolerance deviation values of the respectivestructural components; and orienting the nozzle in the linear dimensionsand the angular plane according to the respective statisticallycalculated nominal closure values and tolerance zones.
 5. The method ofclaim 4, wherein the step of orienting comprises compensating for acuvette sidewall draft.
 6. The method of claim 4, wherein the solidparticles are accumulated against an interior wall of each reactionvessel by action of a magnet array, and wherein the step of orientingincludes orienting according to statistically calculated nominalhorizontal closure values and tolerance values associated with themagnet array.
 7. The method of claim 4, wherein the step of orientingcomprises compensating for the effect of gravity on a stream ofresuspension liquid.
 8. The method of claim 7, wherein the step ofcompensating for the effect of gravity comprises further identifying therate at which the resuspension liquid flows and the diameter of eachnozzle.
 9. The resuspension nozzle module of claim 1, further comprisinga buffer zone defined within the housing intermediate the mountingrecess and the plural channels, the buffer zone enabling pressureequalization between the plural channels.